Lyme disease, a tick-transmitted, immune-mediated, epidemic disorder in children and adults, usually begins in summer with a characteristic skin lesion, erythema chronicum migrans, that may be followed weeks to months later by meningoencephalitis, peripheral neuritis, myocarditis, or by migratory, intermittent or chronic arthritis. We plan to define the natural history of this illness--its prognosis and treatment--etiology, vector, and pathogenesis. To accomplish these objectives, a network of primary physicians has been established to refer patients with recent onset of the illness. The natural history of the disease will be described from the serial examination of these patients. The possible pathogenetic role and interactions between circulating immune complexes, lymphocyte function, and immunogenetic determinants will be explored in selected patients. Epidemiologic field studies of patients, the implicated vector, I. dammini, and its animal hosts and environment will be done on 2 islands to determine the natural cycle of the disease. In an effort to identify the causative agent, ticks collected from the field will be identified by stage and species, pooled, and inoculated into monkeys, Peromyscus leucopus, and embryonated hens' eggs. Tick pools and their salivary glands will be reacted with convalescent sera by indirect immunofluorescence and by radioimmunoassay. If the agent can be identified, a serologic test for diagnosis will be developed, and attack rates will be determined within sample human and animal populations. The results would provide the basis for decisions about control measures.